放射外科联合替莫唑胺治疗对大鼠垂体腺瘤GH3、MMQ细胞侵袭性及内分泌的影响  

Effect of radiosurgery combined with temozolomide therapy in vitro on invasion and endocrine function of GH3 and MMQ cells in rat pituitary adenomas

作　　者：林益光[1] 刘晓民[1] 张志远[1] 王国开[1] 康春生[1] 徐德生[1] 

机构地区：[1]天津医科大学第二医院神经外科伽玛刀治疗中心,天津300211

出　　处：《中华神经医学杂志》2016年第3期267-273,共7页Chinese Journal of Neuromedicine

基　　金：天津市自然科学基金一般项目（13JCYBJC24000）;天津市教委科研计划项目（20090131）;天津市卫生局科技基金（2011KZ95）

摘　　要：目的通过体外实验的方式研究放射外科结合替莫唑胺治疗对大鼠垂体腺瘤细胞侵袭性及内分泌功能的影响。方法将体外常规培养的大鼠垂体腺腺瘤GH3、MMQ细胞分为对照组、10Gy放射组、20Gy放射组、替莫唑胺组、联合治疗组，以边缘剂量为10Gy、20Gy的伽玛刀照射细胞为10Gy、20Gy放射组。将未照射细胞设为对照组，20Gy放射照射后GH3、MMQ细胞继续培养12 h，再分别以250 μmol/L和615 μmol/L替莫唑胺处理24 h为联合治疗组。未照射GH3、MMQ细胞分别加入250 μmol/L和615 μmol/L替莫唑胺作用24 h为替莫唑胺组。应用RT-PCR、Western blotting分别检测细胞基质金属蛋白酶（MMP）-9、血管内皮生长因子（VEGF）mRNA和蛋白的表达；应用Elisa试剂盒检测GH3、MMQ细胞培养液泌乳素（PRL）、生长激素（GH）以及MMQ细胞培养液中PRL的含量。结果与对照组比较，10Gy、20Gy放射组GH3、MMQ细胞MMP-9、VEGF mRNA和蛋白的表达，GH3细胞PRL和GH的分泌量，MMQ细胞PRL的分泌量均降低，且20Gy放射组细胞MMP-9、VEGF mRNA和蛋白的表达，GH3细胞PRL和GH的分泌量，MMQ细胞PRL的分泌量均低于10Gy放射组，差异有统计学意义（P〈0.05）；联合治疗组细胞MMP-9、VEGF mRNA和蛋白的表达，GH3细胞PRL和GH的分泌量，MMQ细胞PRL的分泌量（0.040±0.006）明显低于10Gy、20Gy放射组（0.130±0.03、0.070±0.008）及替莫唑胺组（0.090±0.008），差异均有统计学意义（P〈0.05）。结论放射外科结合替莫唑胺对大鼠垂体腺瘤GH3、MMQ细胞系的侵袭性及内分泌功能有明显的抑制作用，并且优于单纯放射治疗及单纯替莫唑胺治疗。Objective To research the effect ofradiosurgery in combination oftemozolomide therapy in vitro on invasion and endocrine function of rat pituitary adenoma cells. Methods Rat pituitary adenoma cell lines GH3 and MMQ were divided into control group, 10 Gy irradiation group, 20 Gy irradiation group, temozolomide treatment group, and radiosurgery in combination of temozolomide group; cells without exposure were used as control group, cells treated with gamma knife radiation respectively with marginal doses of 10 and 20 Gy （all to the 99% isodose line） were used as 10 Gy irradiation group and 20 Gy irradiation group, cells treated with 250 μmol/L and 615 μmol/L temozolomide for 24 h after 20 Gy radiation were used as radiosurgery in combination of temozolomide group, and cells treated with 250 μmol/L and 615 μmol/L temozolomide for 24 h were used as temozolomide treatment group. Real time-PCR and Western blotting were employed to measure the mRNA and protein expressions of matrix metalloproteinase （MMP）-9 and vascular endothelial growth factor （VEGF）; and secretion of prolactin （PRL） and growth hormone （GH） was detected by ELISA. Results As compared with the control group, the 10 Gy irradiation group and 20 Gy irradiation group had significantly lower mRNA and protein expressions of MMP-9 and VEGF, and secretion of PRL and GH （P〈0.05）; and these levels in the 20 Gy irradiation group were significantly lower than those in the 10 Gy irradiation group （P〈0.05）; As compared with the 10 Gy irradiation group, 20 Gy irradiation group, and temozolomide treatment group, the radiosurgery in combination of temozolomide group had significantly lower mRNA and protein expressions of MMP-9 and VEGF, and secretion of PRL and GH （P〈0.05） Conclusion Gamma knife radiosurgery combined temozolomide could significantly inhibit the invasive ability and endocrine function of rat pituitary adenoma cell lines GH3 and MMQ, which has better effect than radiotherapy or temozolomide treatment alone.

关 键 词：放射外科 伽玛刀 替莫唑胺 垂体腺瘤 联合治疗 侵袭性 

分 类 号：R736.4[医药卫生—肿瘤]